Phosphodiesterase 4D, miR-203 and selected cytokines in the peripheral blood are associated with canine atopic dermatitis

Abstract

Canine Atopic Dermatitis (AD) is a common complex and multifactorial disease involving immune dysregulation, genetic predisposition, skin barrier defects, environmental factors and allergic sensitization. To date, diagnosis of canine AD relies on a combination of patient history, clinical examination, allergy testing and response to diet trials/therapies with no reliable biomarkers available to distinguish AD from other diseases with similar clinical presentations. A handful of studies to identify potential biomarkers in the peripheral blood of AD dogs and healthy controls have been performed with some showing inconsistent and contradictory results. In this study, we, for the first time, report statistically significant increases in expression of phosphodiesterase 4D (PDE4D) gene in peripheral blood mononuclear cells (PBMCs) and miR-203 in plasma from AD dogs compared to healthy controls. In addition, we report a statistically non-significant change of the CD4 + /CD8 + ratio, a dramatic decrease of three gene markers (PIAS1, RORA and SH2B1) as well as a panel of differential expression of cytokines in AD dogs in comparison to the healthy controls. Our study provides important insight into the complexities of canine AD, and further studies to verify the specificity of these findings for canine AD at a larger-scale are warranted.

Altered plasma cytokines in dogs with atopic dermatitis

“…In addition to the aforementioned discussion on possible roles of IL‐7 in AD, in the presence of GM‐CSF, IL‐7 supports survival of eosinophils in combination with IL‐4 61 . However, IL‐4 concentrations did not differ between atopic and control dogs in our study and also in others 29,30 . Another effect of IL‐7 is increased secretion of GM‐CSF from eosinophil granules of asthmatic patients, enhancing the allergic response in atopic diseases.…”

“…Previous similar studies that compared atopic to control dogs were inconclusive, with increased TNFa in plasma and increased IFNc in serum, and nonsignificant results about plasma IFNc and serum TNFa. 29,30 Our atopic Staffordshire results may reflect a chronic phase of the disease or a breed-specific effect. It also may indicate a breed-related correlation between elevated IL-7 and IFNc in Staffordshire breeds, in a similar way to human Vogt-Koyanagi-Harada disease, a multisystem autoimmune disease in which serum IL-7 is increased and promotes in vivo expression of IFNc.…”

Cutaneous microRNA expression in healthy Labrador and Golden retrievers and retrievers with allergic and inflammatory skin diseases

“…41 Two other studies recently evaluated miRNAs in atopic dogs. 34,35 In one study, miR-39, miR-203 and miR-483 were evaluated, 34 all miRNAs outside the remit of our study. Both miR-203 and miR-483 were significantly upregulated.…”

“…However, other studies evaluating miRNAs for cAD also had small specimen numbers. 34,35 Another limitation was the retrospective nature of sample collection from diseased dogs. A diagnosis of allergic dermatitis was assumed, when histopathological findings matched history and clinical signs reported by the submitting veterinarian, and it was not necessarily confirmed by a thorough diagnostic work-up.…”

“…33 To the best of the authors' knowledge to date, there are only few published studies investigating miRNAexpression in the skin of allergic dogs. 34,35 A specific miRNA expression in canine allergic dermatitis may be of great interest as a biomarker for the diagnosis and therapy of allergies in the dog.…”